Many hormones, growth factors and neurotransmitters stimulate the production of inositol 1,4,5-trisphosphate evoking the release of calcium from intracellular stores. The depletion of these intracellular calcium stores subsequently activates a voltage-independent plasma membrane calcium influx in many cell types. This store-operated calcium influx is essential for generating prolonged cytosolic calcium signals and for refilling the intracellular calcium stores. Recent studies suggest that the store-operated calcium channels may be encoded by the trp family of genes, which show structural homology to voltage-operated channels. Ankyrin-like repeats encoded by trp may be involved in regulating the channel by a direct interaction with the inositol 1,4,5-trisphosphate receptor on the intracellular calcium stores.